Our lives are full of instances where have to hold ourselves back. We stop ourselves from eating that tempting slice of cake to avoid putting on weight. We bite our tongues to avoid insulting our friends. We slam on the brakes to avoid killing a pedestrian. To quote Yoda: “Control! Control! You must learn control.”

People with drug problems clearly have a problem with this. Their ability to resist their own impulses falters at the promise of the next hit. Now, scientists are starting to understand the changes in the brain that underlie these problems.

Karen Ersche from the University of Cambridge found that drug users have abnormalities in parts of the brain that are important for inhibiting unwanted actions. These same anomalies even exist in the brains of their siblings, who don’t have any drug problems themselves. They could act as a marker for people who are vulnerable to addiction. “Our findings provide further evidence for drug addiction being a brain-based disorder,” says Ersche.

This is far from the first study to examine the brains of drug users. But it’s never been clear whether changes in such brains were caused by drugs, or made people vulnerable to addiction in the first place. Both are possible. Stimulant drugs typically act on parts of the brain involved in motivation, and interfere with those that inhibit our impulses. But these effects could be worse if these neural circuits are already weak.

To separate these possibilities, Ersche studied 50 volunteers who had a long history of drug abuse. She compared them to their siblings, who had no drug problems, and to 50 unrelated volunteers who were also drugs-free. All of the recruits sat through a stop-signal test – a commonly used way of measuring self-control. Volunteers have to respond as quickly as possible to a stream of on-screen symbols – say, by pressing a key. If they hear a tone, which pops up unpredictably, they have to restrain themselves. (Try it yourself here).

The drug users struggled with the test compared to the unrelated volunteers, and needed more time to withhold their responses. Critically, their siblings fared just as badly, even though they weren’t using drugs. This strongly suggests that poor self-control isn’t the result of the drugs themselves, but of a shared (and probably inherited) vulnerability. “If you have brain with existing problems, the drugs have an easier play. It’s easier for them to take over,” says Ersche.

Ersche found the same pattern when she looked at her volunteers’ brains. First, she focused on their white matter tracts – the fibres that transmit signals from one area to another. These are the brain’s communications network, and their density indicates how good different areas are at shuttling information between them.

These connections were weaker among both the drug users and their relatives, compared to the healthy unrelated volunteers. The fibres were particularly sparse around the right inferior frontal cortex (IFC), an area involved in controlling our inhibitions. These abnormalities were linked to the volunteers’s scores on the stop-signal test – the weaker the connections, the slower their reaction times. With its communication lines weakened, the IFC was less able to exert its suppressive influence.

The siblings also shared anomalies in the size of some brain areas. Their putamens and medial temporal lobes were bigger, and their posterior insulas were smaller. All of these areas have been implicated in learning and memory. “This may be an indicator of an enhanced propensity to form habits,” says Ersche.

From these results, a cohesive picture emerges. Some parts of the brain are larger, increasing the attractiveness of potential rewards, and the odds of habitual, addictive behaviour. The IFC, which would normally suppress such desires, has less of a say because the fibres connecting it to other parts of the brain are weaker. It’s like having a mob of reckless friends who are egging each other on over fast broadband connections, while their sensible parents send them words of caution on a dial-up modem.

This is uncannily similar to what happens in the teenage brain, where areas associated with reward mature before the prefrontal areas that exercise restraint. Other scientists have suggested that this gap in timing explains why teens are so prone to risky and impulsive behaviours. They’re not making thoughtless decisions – they simply weigh risks and rewards in a different way to adults. Perhaps people who are vulnerable to addiction never grow out of this asymmetry between desire and inhibition. “It does look like a developmental problem,” says Ersche, “but we really need to compare these brains to those of adolescents to know for sure.”

“This is a very important and well-designed study,” says Susan Tapert from the University of California, San Diego. She adds, “It will be important to understand how the non-drug dependent volunteers were able to avoid drug problems given same brain features as their siblings.”

This is a key point. Drug dependence runs in families, and it is clearly influenced by a person’s genes. But genes do not determine behaviour; they merely influence it. The non-addicted siblings in Ersche’s study illustrate the point beautifully. “They share so much,” says Ersche. “They have the same vulnerabilities as their drug-dependent brothers and sisters. They had a lot of domestic violence and troubled childhoods but they didn’t get into drugs. Their average age was 33. They may have had many opportunities to develop dependence, but they didn’t.”

Perhaps the other one had environmental influences that set them down a different path. Perhaps they also had inherited some “resilience factors” that their siblings did not. In an earlier study with some of the same siblings, Ersche found that all of them are more impulsive, but only the drug users were “sensation-seekers”. These are subtly different traits. “Impulsive people act on the spur of the moment,” Ersche explains, “but sensation-seekers crave excitement and adventure. In contrast to the drug-dependent individuals, their siblings do not seem to crave for excitement and sensations, which might have protected them from taking drugs in the first place.

In the meantime, Ersche’s study suggests that the white fibre tracts around the IFC could be used as a marker for vulnerability to addiction. That’s useful for two reasons. We could use it to identify people who are most at risk of abusing drugs, before they actually encounter any problems. We could also see if people can strengthen the connections in this critical area. Many scientists have developed programmes for improving self-control at an early age. Monitoring the IFC’s white matter could provide an objective way of measuring whether those programmes are working. As Tapert says, “We might be able to modify these risky brain characteristics, to see if the misuse of drugs can be reduced.”

Comments (4)

G

Interesting. That stop-signal test sounds remarkably like the one I took for ADD diagnosis. With ADD, you start out responding correctly, but as it continues, your responses get worse and worse (they tested accuracy, time to response, and persistence).

How exactly does addiction work? I thought it involved a physiological dependence not just a lack of self control. If siblings share similar socioeconomic, family background, brain scans, and stop-signal performance, but not drug addiction it would seem that those things do not determine drug addiction. Further it is dubious to draw any conclusion from a data set of 50 or 100 that draws on self reported data.

I searched this post in vain for exactly what ‘drugs’ were involved in the study–that’s an extremely broad and diverse category, even for drugs of abuse–and found only a single indirect mention of ‘stimulant drugs’ (which I see is also specified in the title of the publication discussed, and the abstract, without further specification).
I don’t think it’s likely to be useful to extrapolate these findings to all addictive drugs, which after all work on very different receptors and synapses, and probably therefore have different underlying causes for addiction.